We investigated the mechanisms of
anti-IgM antibody-induced cell death in a recently established human surface IgM+ IgD+ B
lymphoma cell line, B104, the growth of which is irreversibly inhibited by
anti-IgM antibody but not by
anti-IgD antibody, and compared it with the cell death of T cells via
TCR/CD3 complex and with the cell death of a murine
anti-IgM antibody-sensitive B
lymphoma cell line, WEHI-231. The rapid time course of B104 cell death and its requirements for de novo macromolecular synthesis and Ca2+ influx suggest that
anti-IgM antibody-induced B104 cell death is an active Ca(2+)-dependent programmed cell death. Moreover,
cyclosporin A rescued B104 cells from this lethal signal, via surface
IgM, suggesting that the intracellular mechanisms involved are quite similar to those of T cell death. DNA fragmentation, which has been reported in
TCR/CD3 complex-mediated T cell death, apoptosis, was not involved in the B104 cell death process, but the possible involvement of
DNA single-strand breaks was suggested. Observations under light microscopy and transmission electron microscopy indicated that the morphologic features of dying B104 cells resembled
necrosis rather than apoptosis. B104 cell death was shown to be quite distinct from that of WEHI-231 in cell death kinetics, the mode of cell death, and the response to
cyclosporin A. These data collectively indicate that the death of B104 cells resulting from surface
IgM cross-linking represents a hitherto undefined mode of programmed cell death.